Light control devices and methods for regional variation of visual information and sampling

ABSTRACT

Exemplary light control devices and methods provide a regional variation of visual information and sampling (“V-VIS”) of an ocular field of view that improves or stabilizes vision, ameliorates a visual symptom, reduces the rate of vision loss, or reduces the progression of an ophthalmic or neurologic condition, disease, injury or disorder. The V-VIS devices and methods may optically move, at a sampling rate between 50 hertz and 50 kilohertz, one or more apertures anterior to a retina between one or more positions anterior to the retina that are non-coaxial with a center of a pupil and a position anterior to the retina that is coaxial with the center of the pupil. Certain of these V-VIS devices and methods may be combined with augmented or virtual reality, vision measurement, vision monitoring, or other therapies including, but not limited to, pharmacological, gene, retinal replacement and stem cell therapies.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of priority to U.S. ProvisionalApplication No. 62/608,039, entitled “LIGHT CONTROL DEVICES AND METHODSFOR NOVEL REGIONAL VARIATION OF VISUAL INFORMATION AND SAMPLING”, filedDec. 20, 2017, which is incorporated herein by reference in its entiretyfor all purposes.

TECHNICAL FIELD

The disclosed embodiments relate to light control devices and methodsfor regional variation of visual information and sampling.

BACKGROUND

The retina is the part of the eye that responds to light from an ocularfield of view and converts the light to signals to begin imageprocessing. Visual processing continues in the brain where the retinalvisual information is integrated spatially, temporally and with ocularmovements to achieve visual perception of the ocular field of view. Anoptical axis is a straight line perpendicular to the front of the eyeand extending through a center of the pupil, defined herein as coaxial.

SUMMARY

In some examples, a light control device is configured to move opticallyone or more apertures anterior to a retina of an eye between one or morepositions anterior to the retina that are non-coaxial with a center of apupil and a position anterior to the retina that is coaxial with thecenter of the pupil. The one or more apertures are moved at a ratebetween 50 hertz and 50 kilohertz, and the light control device producesa regional variation of visual information and sampling of an ocularfield of view.

In additional examples, anterior to the retina can include one ofextraocular, intracorneal or intraocular placement. Further, the lightcontrol device can move the one or more apertures electro-opticallythrough one or more see-through displays placed anterior to the retina.The one or more see-through displays of the V-VIS device can be furtherconfigured to display at least one of an augmented reality image, avirtual reality image, or a combination of an augmented and virtualreality images.

The light device can also include one or more waveguides, and the lightcontrol device can move the one or more apertures using the one or morewaveguides. In further examples, the one or more waveguides can bearranged in at least one of vertically stacked in layers, adjacent toone another in a single layer, or holographically multiplexed.

In some examples, the one or more see through displays can include oneor more transparent carrier layers, and each of the transparent carrierlayers can include one or more active optical elements. The lightcontrol device can also include an electrical component coupled to eachof the transparent carrier layers. The electrical component can directan electrical current through each of the transparent carrier layers,and the directed electrical current can electrify the one or more activeoptical elements to create and move the one or more apertures. In someinstances, two or more of the transparent carrier layers can bevertically stacked in more than one plane, and the one or more activeoptical elements in each of the two or more transparent carrier layerscan become less transparent than the aperture when electrified. The oneor more apertures can be defined by at least one of: (i) an area withoutthe one or more active optical elements surrounded by an area in eachtransparent carrier layer with the one or more active optical elements;or (ii) an area without activation of the one or more active opticalelements surrounded by an area in each transparent carrier layer withactivation of the one or more active optical elements. The spatiallocation of each of the one or more apertures in each carrier layer canbe displaced relative to one another.

In additional examples, the light control device can be configured tomove the one or more apertures by off-axis projection. Further, thelight control device can be utilized to produce the regional variationof visual information and sampling of the ocular field of view for atleast one of vision, screening, customization, calibration, visionmeasurement, or vision monitoring.

Further, in some examples, the regional variation of visual informationand sampling of the ocular field of view can produce at least one of:(i) an improvement of vision in an eye or in both eyes of a subject;(ii) a stabilization of vision in the eye or in both of the eyes of thesubject. (iii) a correction of an ophthalmic or neurologic condition;(iv) an amelioration of a visual symptom in the eye or in both of theeyes of the subject with an ophthalmic or neurologic condition, disease,injury or disorder; (v) a reduction of a rate of vision loss in the eyeor in both of the eyes of the subject with a vision loss from anophthalmic or neurologic condition, disease, injury or disorder; (vi) areduction of a rate of progression of an ophthalmic or neurologiccondition, disease or disorder in the eye or in both of the eyes of thesubject with an ophthalmic or neurologic condition, disease or disorder;(vii) a vision measurement or monitoring of the eye or both of the eyesof the subject.

The light control device also can include one or more cameras and atleast one processor functionally coupled to the one or more cameras. Theat least one processor can be configured to execute softwareinstructions to capture light from at least one of peripheral to, above,below or behind an eye, a fellow eye, or both eyes of a subject, anddeliver the light to the retina of the eye, the fellow eye, or both eyesof the subject.

Further, the light control device also can include one or moremicrophones and at least one processor coupled to the one or moremicrophones. The at least one processor can be configured to executesoftware instructions to convert an audible speech to a text in apreferred language and to display the text within a field of view of asubject. In some examples, the light control device also can include oneor more light emitting diodes placed around the perimeter of the fieldof view, and the processor can be further configured to execute thesoftware instructions to energize selectively the one or more lightemitting diodes to indicate a direction from which the audible speech isproduced.

In further examples, a method includes utilizing a light control device.The device is configured to move optically one or more aperturesanterior to a retina of an eye between one or more positions anterior tothe retina that are non-coaxial with a center of a pupil and a positionanterior to the retina that is coaxial with the center of the pupil. Theone or more apertures are moved at a rate between 50 hertz and 50kilohertz, and the light control device produces a regional variation ofvisual information and sampling (V-VIS) of an ocular field of view.

Additionally, in some examples, anterior to the retina can include oneof extraocular, intracorneal or intraocular placement, and the lightcontrol device can be configured to electro-optically move one or moreapertures through one or more see-through displays placed anterior tothe retina to produce the regional variation of visual information andsampling of the ocular field of view for at least one of vision,screening, customization, calibration, vision measurement, or visionmonitoring. The light control device can also be configured to produceat least one of an improvement of vision in an eye or both eyes of asubject, a stabilization of vision in the eye or in both of the eyes ofthe subject, a correction of an ophthalmic or neurologic condition, anamelioration of a visual symptom in the eye or both of the eyes of thesubject with the ophthalmic or neurologic condition, a disease, aninjury or a disorder, a reduction of a rate of vision loss in the eye orboth of the eyes of the subject with vision loss from the ophthalmic orneurologic condition, disease, injury or disorder, a reduction of a rateof progression of the ophthalmic or neurologic condition, disease ordisorder in the eye or both of the eyes of the subject with theophthalmic or neurologic condition, disease, or disorder, a visionmeasurement of an eye or both eyes of a subject, or a vision monitoringof the eye or both of the eyes the a subject.

The method also can include utilizing the light control device toproduce at least one of an augmented reality image, a virtual realityimage, or a combination of an augmented and virtual reality images. Inother examples, the method also can include treating an eye using thelight control device, and at a time prior to the treatment, during thetreatment, or after the treatment, administering at least one of agenetic, epigenetic, optogenetic, retinal replacement or stem celltherapy for treating an ophthalmic or neurologic condition, disease,injury or disorder.

In further examples, the method can include treating an eye using thelight control device, and at a time prior to the treatment, during thetreatment, or after the treatment, administering a therapeuticallyeffective amount of an anti-angiogenesis agent administered via at leastone of an intravitreal injection, orally, topically, intraretinally, viaan implant or via iontophoresis, wherein the combination therapy is fortreating or ameliorating a symptom of a neovascular ophthalmiccondition, disease, injury or disorder.

The method also can include treating an eye using the light controldevice, and at a time prior to, during, or after the treatment using thelight control device, administering, topically, intraretinally, viaintravitreal injections, via implants, or via iontophoresis, and fortreating an ophthalmic or neurologic condition, disease, injury ordisorder a therapeutically effective amount of at least one of: (i) anintraocular pressure-lowering agent comprising a miotic, an alpha oralpha/beta adrenergic agonist, a beta-blocker, a Ca2+ channel blocker, acarbonic anhydrase inhibitor, a cholinesterase inhibitor, aprostaglandin agonist, a prostaglandin, a prostamide, or a cannabinoid;(ii) a retinal cell- or cortical cell-neuroprotective orneuroregenerative agent comprising a rho-kinase inhibitor, an adenosinereceptor agonist, a glutamate antagonist, a neurotrophic factor, or aneurotrophic factor regulator; or (iii) a combination of the intraocularpressure-lowering agent and the retinal cell- or corticalcell-neuroprotective or neuroregenerative agent. The ophthalmic orneurologic condition, disease, injury or disorder can include aglaucoma, a macular degeneration, an optic nerve atrophy, an optic nerveinjury, an autoimmune neuro-degenerative disorder, or a cerebrovascularaccident.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a flowchart showing the neural processing that results invisual perception, according to some examples.

FIG. 2 illustrates an example of a light control device comprising atransparent reflective diffuser display upon which moving apertures canbe formed by off-axis projection, according to some examples.

FIG. 3A is a diagram of a light control device, comprising asubstantially transparent liquid crystal or other optically activatedmaterial contained in a thin film defined herein as a carrier layer orcarrier layer unit, showing a moving aperture at a single positionduring a single sampling time interval, according to some examples.

FIG. 3B is an illustration of a light control device comprising verticalstacking of multiple carrier layer units of FIG. 3A, each containingoptically active material, and showing five possible aperture positionsused to create a moving aperture effect in accordance with someexamples.

FIG. 4A is a side and top view of an eye showing the invented carrierlayers of FIG. 3B within a light control device, comprising a pair ofspectacles and a waveguide, and a moving aperture at one position duringa single sampling time interval in accordance with some examples.

FIG. 4B is a side view of an eye with a light control device comprisinga contact lens and an off-axis projection system of FIG. 2, creating amoving aperture herein depicted at one position during a single samplingtime interval in accordance with some examples.

FIG. 4C is a side view of an eye with a light control device comprisinga corneal inlay showing a moving aperture at one position during asingle sampling time interval in accordance with some examples.

FIG. 4D is a side view of an eye with a light control device comprisingan intraocular lens implant showing multiple moving apertures in oneexemplary configuration during a single sampling time interval inaccordance with some examples.

FIG. 5 depicts a light control device comprising a pair of spectaclesviewed at different points in time, in accordance with some examples.

FIG. 6 depicts a light control device comprising a remotely accessibledevice, according to some examples.

DETAILED DESCRIPTION

Among those benefits and improvements that are disclosed herein, otherobjects and advantages of the exemplary embodiments can become apparentfrom the following description taken in conjunction with theaccompanying figures. Detailed exemplary embodiments are disclosedherein; however, it is to be understood that these disclosed exemplaryembodiments are merely illustrative and may be embodied in variousforms. In addition, each of the examples given in connection with thevarious embodiments is intended to be illustrative, and not restrictive.Any alterations and further modifications of the features illustratedherein, and any additional applications of one or more of the principlesillustrated herein, which can normally occur to one skilled in therelevant art and having possession of this disclosure, are to beconsidered within the scope of the disclosed exemplary embodiments.While the description herein teaches certain features as applied tovarious embodiments, it will be understood that various omissions,substitutions, and changes in the form and details of the device ormethod illustrated can be made without departing from the spirit of thedisclosure. As will be recognized, certain of the exemplary embodimentsdescribed herein can be embodied within a form that does not provide allof the features and benefits set forth herein, as some features can beused or practiced separately from others. All changes which come withinthe meaning and range of equivalency of the claims are to be embracedwithin their scope.

Throughout the specification, the following terms take the meaningsexplicitly associated herein, unless the context clearly dictatesotherwise. The phrases “In one embodiment” and “in some embodiments” asused herein do not necessarily refer to the same embodiment(s), thoughit may. Furthermore, the phrases “in another embodiment” and “in someother embodiments” as used herein do not necessarily refer to adifferent embodiment, although it may. Thus, as described below, variousof the exemplary embodiments may be readily combined, without departingfrom the scope or spirit of the exemplary embodiments.

In addition, as used herein, the term “or” is an inclusive “or”operator, and is equivalent to the term “and/or,” unless the contextclearly dictates otherwise. The term “based on” is not exclusive andallows for being based on additional factors not described, unless thecontext clearly dictates otherwise. In addition, throughout thespecification, the meaning of “a,” “an,” and “the” include pluralreferences. The meaning of “in” includes “in” and “on.”

A. Introduction

The specification describes, among other things, exemplary devices andmethods that perform a regional variation of visual information andsampling (e.g., V-VIS) of an ocular field of view by optically movingone or more apertures anterior to a retina between one or more positionsanterior to the retina that are non-coaxial with a center of a pupil anda position anterior to the retina that is coaxial with the center of thepupil. The exemplary V-VIS devices described herein correspond to, andfunction as, light control devices that produce the regional variationof visual information and sampling. Further, and as described herein,“anterior to the retina” includes one of extraocular, intracorneal, orintraocular placement, and the one or more apertures are moved at a ratebetween 50 hertz and 50 kilohertz.

Certain of the exemplary V-VIS devices and methods can be utilized forat least one of screening for use of V-VIS, customization of V-VIS,calibration of V-VIS, V-VIS vision measurement, V-VIS vision monitoring,or any combination thereof. One or more of the exemplary V-VIS devicesand methods can improve and/or stabilize vision in an eye or both eyesof a subject and/or correct an ophthalmic or neurologic condition. Insome embodiments, the V-VIS delivery (e.g., using the exemplary V-VISdevices and methods described herein) of visual information from anocular field of view to the retina also ameliorates a visual symptom orreduces the rate of vision loss or reduces the progression of visionloss or functionally measures vision, including but not limited to thevisual processing effect of an ophthalmic or neurologic condition,disease, injury or disorder, or monitors vision.

Further, one or more of the exemplary V-VIS devices and methodsdescribed herein can provide a novel delivery of visual information froman ocular field of view to different areas of the retina at a rapidenough rate to overcome limitations of conventional light controldevices, as well as limitations of natural visual processing andperception, to improve vision in subjects with decreased vision or anophthalmic or neurologic condition or any combination thereof. Incontrast to conventional devices and methods for delivering visualinformation from an ocular field of view to the retina, one or more ofthe exemplary V-VIS devices and methods can provide improved monocularand/or binocular visual outcomes and/or fewer visual adverse effectsand/or more patient convenience and/or compliance with treatments forophthalmic and/or neurologic conditions. In further contrast to someconventional devices, such as retinal prostheses, certain of theexemplary V-VIS devices and methods can be utilized with existing and/ornatural neural circuitry in the retina and/or brain, do not requirereplacement of natural neural circuitry and do not interfere with normalnatural vision processing mechanisms.

Examples of the V-VIS devices and methods described herein includeextraocular devices, such as, but not limited to, spectacles, accessorydevices for spectacles, heads up displays, visors, contact lenses,accessory devices for contact lenses, and viewing screens, such as, butnot limited to, remotely accessible-televisions, -computers, and -mobiledevices, corneal inlays, intraocular devices, intraocular lenses andintraocular lens accessories that are configured as V-VIS light controldevices. The exemplary V-VIS devices and methods described herein canproduce V-VIS in combination with augmented reality and/or virtualreality or can be part of an augmented and/or virtual reality system.

In some embodiments, one or more of the exemplary V-VIS devices andmethods can be combined with other treatments for retinal and/orneurologic conditions, diseases, injuries and disorders including, butnot limited to, genetic therapy, epigenetic therapy, optogenetictherapy, retinal replacement therapy, stem cell therapy and/orpharmacological agents, including but not limited to, anti-angiogenesisagents, intraocular pressure-lowering agents, neuroprotective agents andneuroregenerative agents.

The exemplary V-VIS devices and methods, as described herein, areconfigured to improve and/or stabilize vision in an eye or both eyes ofa subject. Some embodiments of the exemplary devices and methodsdescribed herein correct an ophthalmic or neurologic condition. In someembodiments, the V-VIS delivery of visual information from an ocularfield of view to the retina also ameliorates a visual symptom of anophthalmic or neurologic condition, disease, injury or disorder,including, but not limited to, age-related macular degeneration (AMD),Stargardt's disease, Bests vitelliform macular dystrophy, alight-induced retinal injury, a cone dystrophy, reverse retinitispigmentosa, myopic macular degeneration, a macular scar, an inheritedretinal disorder, diabetic retinopathy (DR), a macular edema, a macularhole, a macular detachment, a macular pucker, a vascular retinaldisorder (including, but not limited to, retinal vein occlusions andCoats' Disease), retinitis pigmentosa, a nutritional retinal disorder,an inflammatory retinal disorder, a glaucoma or other neuro-retinal organglion cell disorder, an autoimmune disorder (including but notlimited to multiple sclerosis and lupus erythematosus), acerebrovascular accident, dyslexia, amblyopia (caused by conditionsincluding, but not limited to, a refractive error, medial opacity orobstruction, or an oculomotor condition, or any combination thereof),presbyopia and ametropia.

Some embodiments of the exemplary devices and methods described hereinreduce, compared to an untreated control group, the rate of vision lossin an eye or both eyes of a subject with a vision loss from anophthalmic or neurologic condition, disease, injury or disorder. Someembodiments of the exemplary devices and methods described hereinreduce, compared to an untreated control group, the progression of anophthalmic or neurologic condition, disease, or disorder. Someembodiments of the exemplary devices and methods described hereinmeasure or monitor vision, including, but not limited to, effects ofophthalmic or neurologic conditions, diseases or disorders on visualprocessing and/or aid screening of subjects for V-VIS and/or acustomization of V-VIS and/or a calibration of V-VIS.

B Exemplary Devices and Methods for Regional Variation of VisualInformation and Sampling

FIG. 1 diagrammatically shows an integration of the various componentsof a visual system, according to some examples. Light carrying visualinformation from an ocular field of view is directed through the eye anddelivered to light sensitive retinal cells that absorb the light andstart processing the visual information. The light sensitive retinalcells convert the light energy to signals that are sent to other retinalcells and the brain where further processing, including but not limitedto, coding, filtering and integration, combined with feedforward andfeedback loops within the retina and brain and to and from extraocularmuscles, results in visual perception.

Some embodiments of the exemplary V-VIS devices and methods of describedherein produce novel delivery of light to the retina. Some embodimentsof the exemplary devices and methods produce variations of sampling oflight within an ocular field of view. In some exemplary embodiments, themovement of one or more apertures anterior to a retina between one ormore positions anterior to the retina that are non-coaxial with a centerof a pupil and a position anterior to the retina that is coaxial withthe center of the pupil vary regionally the ocular field of view and/orthe retinal area (or areas) to which an ocular field of view ispresented. In some exemplary embodiments, the regional variation of theocular field of view and/or the retinal area/s to which an ocular fieldof view is delivered by the one or more of the exemplary V-VIS devicesand methods is determined by at least one of the following: the diameterof the one or more apertures, the transparency of the one or moreapertures to selective wavelengths, the number of apertures, thediameter of the area within which the one or more apertures are moved,the positions to which the apertures are moved, the order in which theapertures are moved to different positions, the transparency toselective wavelengths of the area or portions of the area outside theone or more apertures and the rate between 50 hertz and 50 kilohertz atwhich the one or more apertures are moved.

In some exemplary embodiments, exemplary V-VIS devices and methods moveone or more apertures that are substantially circular or hexagonal orelliptical or oval or square or rectangular or of any desired shape orany combination thereof. In some embodiments, exemplary V-VIS devicesand methods move one or more apertures that are configured to have aconstant or adjustable diameter, and/or greatest diameter, ranging from0.1 mm to 4 mm. In some embodiments, exemplary V-VIS devices areconfigured to move one or more apertures within an area having aconstant or adjustable diameter, and/or greatest diameter, ranging from0.2 mm to 10 mm. In some embodiments, exemplary V-VIS devices andmethods are configured to move the one or more apertures to positionsthat are partially overlapped, not overlapped or any combinationthereof. In some embodiments, the positions to which the apertures aremoved overlap areas outside the pupil under photopic or mesopic orscotopic illumination conditions or any combination thereof. In someembodiments, under low light illumination conditions, such as mesopicand/or scotopic conditions, electronic illumination enhancement methodsknown to those skilled in the art are employed. Some embodiments of theexemplary V-VIS devices are configured to move each of the one or moreapertures in a pre-determined order, including, but not limited to,alternately, randomly, sequentially through all positions, in any otherdesired order or in any combination thereof.

In some embodiments, the exemplary V-VIS devices and systems deliverlight with visual information from an ocular field of view to retinalcells with a duration of presentation, herein called a V-VIS samplinginterval (“SI”), through each of the one or more apertures that is ofsufficient duration to enable perception of the ocular field of viewafter further processing in the retina and brain. In some embodiments,V-VIS is accomplished by changing the position of one or more aperturesat a rate between 50 hertz and 50 kilohertz, and not allowing theaperture to persist in any one position for more than one V-VIS SI. Insome embodiments of the exemplary V-VIS devices and methods describedherein, the SI is a time interval lasting between 0.02 ms and 20 ms.

The V-VIS sampling rate (“SR”) of the one or more apertures is definedherein as the number of times per second that each SI is completed,i.e., the number of times per second that each aperture or one or moreapertures are moved to each of the selected positions. In someembodiments, the SR is a rate between 50 hertz and 50 kilohertz. A V-VISsampling cycle (“SC”) is defined herein as the sequence of aperturepositions. In some embodiments, the V-VIS sampling cycle includes someselected positions to which each aperture or one or more apertures aremoved more than one time during the sampling cycle.

In some embodiments, described herein, the exemplary V-VIS methods anddevices are configured to produce an SR or variable SRs based on thespeed of fixational eye movements, including, but not limited to,microsaccades, drifts and tremor. The speed of fixational eye movementsoften is modified by ophthalmic and/or neurological conditions,diseases, injuries or disorders.

In some embodiments, the exemplary V-VIS devices and methods and devicesmove the one or more apertures at an SR rate that is sufficiently rapidto enable stable perception. In some embodiments of the exemplary V-VISmethods and devices deliver light with visual information from an ocularfield of view to retinal cells with a duration of presentationcustomized for an eye or both eyes of a subject. In some embodiments,the exemplary V-VIS devices and methods and devices move the one or moreapertures at different rates for different eyes and/or subjects toenable stable perception without the perception of flicker by thesubject. In some, the exemplary V-VIS devices and methods and devicesmove the one or more apertures at different rates for different eyesand/or subjects to enable stable perception without stroboscopic and/orphantom array effects. In some embodiments, the exemplary V-VIS devicesand methods and devices move the one or more apertures at differentrates for different eyes and/or subjects to enable stable perceptionwithout triggering adverse effects, including, but not limited to,headaches, migraines, cognitive defects and/or photosensitive epilepsy.

In some embodiments, the exemplary V-VIS devices and methods and devicesmove the one or more apertures at different rates for different eyesand/or subjects, depending on age and/or type and/or severity of anophthalmic and/or neurologic condition, disease, injury or disorderand/or other factors. In some embodiments, a delivery of light by theexemplary V-VIS methods and devices is configured to be adjustable. Insome embodiments, the exemplary V-VIS methods and devices deliver lightwith visual information from an ocular field of view to retinal cellswith a duration of presentation through each of the one or moreapertures that initially is too rapid to enable visual perception by aneye and/or both eyes of a subject, but is configured to allowadjustability of the SR, so that, upon slowing of the SR, the SR atwhich visual perception first becomes possible can be determined for agiven eye and/or both eyes of a subject and depends upon variousfactors, including but not limited to, age and type or stage ofinfirmity of a subject. In some embodiments, the exemplary V-VIS methodsand devices are configured for calibration of V-VIS treatment andstaging of an eye and/or both eyes of a subject with an ophthalmic orneurological condition, disease, injury or disorder. In someembodiments, the exemplary V-VIS methods and devices are configured tomonitor improvement in an eye and/or both eyes with an ophthalmic orneurologic condition, disease, injury or disorder after V-VIS treatmentor after conventional therapy or after a combination thereof. Forexample, in some embodiments, the average SR required for visualperception in eyes with a certain condition, disease, injury or disorderis slower than the average SR required for visual perception in matchedcontrol eyes without that condition, disease, injury or disorder andincreases with visual improvement after V-VIS therapy or after othertherapy or after a combination thereof.

In some embodiments, the V-VIS devices and methods can be combined witha method or device for visual testing known to those skilled in the artof visual testing including, but not limited to, visual acuity testing,contrast sensitivity testing or perimetry, to distinguish visionproblems caused by visually significant defocus of light at the retinafrom vision problems due to other causes, including, but not limited tofunctional or structural causes. Vision problems related to retinaldefocus and/or refractive and/or accommodative errors are correctedand/or diminished with utilization of some embodiments of the exemplaryV-VIS methods and devices described herein at a speed within a range ofspeeds that are normal for subjects with refractive errors and/oraccommodative errors but without other ophthalmic or neurologicconditions, diseases, injuries or disorders. In some embodiments, theexemplary V-VIS methods or devices can be combined with a visual acuitytesting method or device known to those skilled in the art of visualtesting and including, but not limited to, visual acuity testing,contrast sensitivity testing or perimetry, to quantify and/or monitorover time the severity of vision impairment caused by defects in visualprocessing in the retina or brain in eyes. Vision impairment related todefects in visual processing in the retina and/or brain are correctedand/or diminished with utilization of some embodiments of the exemplaryV-VIS devices and methods described herein, e.g., as applied to subjectsat a speed within a range of speeds different from that applied to othersubjects without defects in visual processing in the retina and/orbrain. Methods described herein include V-VIS in combination with othermedical or surgical treatments.

Some embodiments of the exemplary V-VIS methods and devices, asdescribed herein, are configured to deliver light to the retina withless myopic and/or hyperopic vergence at the retina. Some embodiments ofthe exemplary V-VIS methods and devices are configured to deliverapproximately collimated light through one or more moving apertures.Some embodiments of the exemplary V-VIS methods and devices move one ormore apertures with diameters that are effective in reducing refractiveerrors in an eye of a subject with ametropia. Some embodiments of theexemplary V-VIS methods and devices move one or more apertures withdiameters that are effective in increasing depth of focus in an eye of asubject with presbyopia. Some embodiments of the exemplary V-VIS methodsand devices decrease refractive errors or increase depth of focus or anycombination thereof, thereby decreasing symptoms of ametropia orpresbyopia or any combination thereof. Some embodiments of the exemplaryV-VIS methods and devices overcome limitations of conventional devicesincorporating a small stationary aperture, including, but not limitedto, visual field restriction, reduction of the amount of light reachingthe retina, contrast sensitivity loss, reduction of stereopsis anddiffraction blurring. Stationary apertures, if sufficiently small tocollimate light and placed in front of a retina, restrict peripherallight rays from being delivered to the retina. In eyes with retinalmacular lesions, a stationary small aperture often does not improvevisual acuity and often causes a reduction in visual acuity byrestricting light to dysfunctional areas of the retina. Stationary smallapertures reduce total illumination and cause less light to reach theretina, thereby reducing visual acuity under low illuminationconditions. Stationary small apertures in only one eye of a subjectinduce anisocoria and produce detrimental interocular differences invisual latency causing hazardous distortions of relative movement. Someembodiments of the exemplary V-VIS devices and systems, as describedherein, overcome the limitations of a stationary small aperture throughstrategic and novel positioning and movement at between 50 hertz and 50kilohertz of one or more apertures, thereby providing betterillumination and better vision in an eye with an ophthalmic orneurologic condition, disease, injury or disorder than conventionaldevices with stationary small apertures.

In some embodiments of the exemplary V-VIS devices and systems, asdescribed herein, the transparency of the one or more apertures toselect wavelengths is constant or adjustable. In some embodiments, thetransparency to select wavelengths of the area outside of the areawithin which the one or more apertures are moved is constant oradjustable.

In some instances, a range of wavelengths of light stimulates each typeof retinal receptor to varying degrees. Yellowish-green light stimulatesboth L and M cones equally strongly, but only stimulates S-cones weakly.Red light stimulates L cones much more than M cones, and S cones hardlyat all. Blue-green light stimulates M cones more than L cones, and Scones a bit more strongly, and is also the peak stimulant for rod cells.Blue light stimulates S cones more strongly and L and M cones moreweakly than red or green light. The brain combines the information fromeach type of receptor to give rise to different perceptions of differentwavelengths of light. Some embodiments of the exemplary V-VIS methodsand devices alter a transparency to select wavelengths of the one ormore apertures and/or of the area outside of the area within which theone or more apertures are moved to change the amount of stimulation ofdifferent types of retinal photoreceptors in an eye or both eyes of asubject for beneficial effects.

Some embodiments of the exemplary V-VIS methods and devices selectivelyalter the transparency of the one or more apertures and/or of the areaoutside of the area within which the one or more apertures are moved towavelengths in the visible spectrum, which ranges from about 400 nm to700 nm. Further, in some instances, chromatic dispersion may causewavelengths in the visible spectrum to have a range of focus of about2.25 diopters. Indices of refraction vary inversely with wavelength;blue rays (short wavelength) are refracted more than red rays (longwavelength). Some embodiments of the exemplary V-VIS methods and devicesselectively alter a transparency to visible wavelengths of the one ormore apertures and/or of the area outside of the area within which theone or more apertures are moved to change the defocus on the retina inan eye or both eyes of a subject.

In some embodiments, the exemplary V-VIS methods and devices describedherein can be configured to deliver light to the retina with less myopicand/or hyperopic vergence at the retina in different areas of the retinato effectively alter the emmetropization process and/or refractivedevelopment of an eye. In some embodiments of the exemplary V-VISdevices and methods can be configured to reduce defocus on a retinalarea within the central retina or outside of the central retina or anycombination thereof to reduce, compared to an untreated control group,the rate of progression of ametropia, including but not limited tomyopia, wherein the central retina is centered on the foveola, maycontain the fovea or parafovea or macula or any combination thereof andmay be of any diameter between 1.5 and 6 mm. In some embodiments, theexemplary V-VIS methods and devices described herein can be configuredto reduce defocus in retinal areas by the diameter, location,chromaticity or any combination thereof of one or more of the movingapertures, of one or more areas without moving apertures or of anycombination thereof.

One or more of the exemplary V-VIS devices and methods, as describedherein, can be configured to improve and/or stabilize vision in an eyeor both eyes of a subject. The vision improvement and/or stabilizationincludes, but is not limited to, improvements and/or stabilization of atleast one of the following of visual acuity (including at least one ofuncorrected and best spectacle-corrected visual acuity for distance,intermediate and near visual acuity), hyperacuity, stereoacuity, vernieracuity, contrast sensitivity, depth of focus, color vision, visualfields, peripheral vision, night vision, face recognition, lightadaptation, dark adaptation, vision-related quality of life, or anycombination thereof.

Further, some embodiments of the exemplary V-VIS devices and methods, asdescribed herein, improve vision by altering visual processing,including, but not limited to, neural coding and/or integration and/orfiltering and/or neuroadaptation and/or perception of an ocular field ofview. Some embodiments of the exemplary V-VIS devices and methodsproduce a novel delivery of light to retinal cells to cause at least oneof the following: (i) alteration of sampling of visual information toenable more correct retinal visual information to be encoded byfunctional retinal cells in multiple retinal areas and transmitted withimproved adaptive and/or predictive sensitization and/or integrationfrom the retina to the brain; (ii) increase in effective and/orspontaneous searching for integration of more visual information; (iii)minimization of the effects of fixation instability and/or defectivegaze selection (iv) beneficial alteration of neural attentionalmodulation; (v) beneficial alteration of the excitatory/inhibitorybalance of the visual systems in both eyes and in the brain, includingbut not limited to altering converging excitatory and inhibitory inputsin one or more visual pathways; (vi) beneficial activation of previouslyunutilized or underutilized sensory, motor, and cognitive systems in theeye and brain; and (vii) beneficial neural adaptation using residualoculomotor and/or sensory plasticity. In some embodiments, the exemplaryV-VIS devices and methods described herein can improve a functioning ofretinal circuitry, including, but not limited to connectivity functionsin visual processing involving photoreceptors and/or ganglion cellsand/or amacrine cells and/or bipolar cells and/or horizontal cellsand/or Müller cells or any combination thereof. In some embodiments, theexemplary V-VIS devices and methods can improve and/or trigger certainprocesses of neural adaptation, including but not limited to, use ofalternate, latent, and/or new natural visual pathways in the retina andbrain. Some embodiments of the exemplary V-VIS devices and methods canimprove visual processing and/or perception without requiringreplacement of existing and/or natural neural circuitry in the retinaand/or brain and without interfering with normal natural visionprocessing mechanisms.

Some embodiments of the exemplary V-VIS devices and methods may producea regional variation of visual information and sampling in combinationwith augmented reality and/or virtual reality, or may be implemented asa part or a component of an augmented and/or virtual reality system.Some embodiments of the exemplary V-VIS devices and methods, asdescribed herein, can produce regional variations of visual informationand sampling in conjunction with at least one of an augmented realityimage, a virtual reality image, or any combination thereof to improveand/or stabilize and/or restore vision. Some embodiments of theexemplary V-VIS devices and methods described herein combine the novelV-VIS delivery to the retina with presentation to the retina of certainvideo, graphical and/or chromatic and/or achromatic additions,deletions, and/or attenuations of light with varying spatial, temporaland/or brightness patterns that are superimposed over the view of anatural scene. Some embodiments of the exemplary V-VIS devices andmethods produce multiple regional variations of chromatic and/orachromatic spatial and/or temporal and/or contrast information of lightwithin an ocular field of view before delivery to retinal cells byregional chromatic and/or achromatic highlighting and/or filteringand/or blocking. Some embodiments of the exemplary V-VIS devices andmethods provide regional visual chromatic and/or achromatic excitatoryand/or inhibitory stimuli to one or both eyes while a subject is viewinga natural visual scene within the ocular field of view during normaldaily activities, in order to improve vision and/or restore vision in asubject with low vision or vision loss from a condition, disease, injuryor disorder. Some embodiments of the exemplary V-VIS devices andmethods, as described herein, can produce regional variations of visualinformation and sampling in conjunction with at least one augmentedreality image or at least one virtual reality image (or any combinationthereof) to alter and/or improve neural coding, filtering, integrationand/or adaptation in the retina and/or brain, resulting in more completeand/or correct perception of a natural visual scene.

In some embodiments of the exemplary V-VIS methods and devices, adelivery of light to retinal cells through the one or more movingapertures decreases cumulative exposure to light over time of retinalcells receiving light during only a portion of each sampling cycle ofthe one or more apertures, when compared to retinal cells receivinglight during a longer portion of the sampling cycle or during the entiresampling cycle or in eyes without a delivery of light by one or more ofthe exemplary V-VIS devices and methods described herein.

In some embodiments of the exemplary V-VIS methods and devices, thedelivery of light decreases cumulative exposure to select wavelengths oflight over time by selective wavelength attenuation to retinal cellsreceiving light through the one or more moving apertures and/or toretinal cells outside the area within which one or more apertures aremoving. In some embodiments, as described herein, one or more of theexemplary V-VIS devices are configured to block selective wavelengths,including, but not limited to, UV wavelengths or blue or blue and violetwavelengths between 415 and 455 nm or other predetermined wavelengths orany combination thereof, which are delivered to the retina through oneor more of the moving apertures or through an area without movingapertures or through any combination thereof during photopic or mesopicor scotopic illumination conditions or any combination thereof.

In some embodiments of the exemplary V-VIS devices and methods, thedecreased cumulative exposure over time of retinal cells to light, withor without selective wavelength attenuation, reduces photostress and/ormetabolic stress and/or phototoxicity in retinal cells. In someembodiments of the exemplary V-VIS devices and methods, the decreasedcumulative exposure over time of retinal cells to light, with or withoutselective wavelength attenuation, can be continued for a period of timeranging from months to years. Decreased cumulative exposure to lightover a period of time ranging from months to years of retinal cells indiseased retinas, including, but not limited to, retinas withage-related macular degeneration can prevent progression of retinal celldamage or drusen formation due to one or more of apoptosis, necrosis,pyroptosis and autophagy. In some embodiments of the exemplary V-VISdevices and methods, selective highlighting of light to viable retinalcells can increase their activation of repair and regenerative processesin damaged retinal areas, thereby also stimulating retinal repair andregenerative processes. In some embodiments of the exemplary V-VISdevices and methods, the regional variation of visual information andsampling, as described herein, can stimulate viable cells' triggering ofcell repair, cell regeneration, or a combination thereof within damagedretinal cells or retinal areas.

Examples of the V-VIS devices described herein include, but are notlimited to, extraocular devices, spectacles, spectacle accessories,contact lenses, contact lens accessories corneal inlays, intraoculardevices, intraocular lenses and intraocular lens accessories that areconfigured, collectively or individually, as V-VIS light controldevices. Some embodiments of the exemplary V-VIS light control devicesand methods described herein can produce regional variations of visualinformation and sampling in combination with augmented reality and/orvirtual reality, or can be part of or incorporated within an augmentedand/or virtual reality system.

Some embodiments of the exemplary V-VIS devices and methods can performoperations that move one or more apertures electro-optically through oneor more see-through displays placed anterior to the retina. Forexplanatory purposes, well-known features of optical technology havebeen omitted or simplified in order not to obscure the basic principlesof the disclosed embodiments. In some embodiments, certain of theexemplary V-VIS devices are configured with components for see-throughmicrodisplays that include, but are not limited to, at least one of alight source, optics, optomechanics, or visual system-optics interfaces.

FIG. 2 illustrates an exemplary V-VIS light control device and methodfor creating a moving aperture, according to some examples. Referring toFIG. 2, a retina of a viewer's eye 10 observes an ocular field of view11 through a transparent display 12. The transparent display can be oneor more of a heads-up display, a visor, a head mounted display, aclip-on lens, an eyeglass lens or eyeglass accessory device. Whileviewing a tree 17, for example, in the natural environment, areas of theviewer's retina are also exposed to a moving aperture 14 that is createdon the surface or within the material of the transparent display, e.g.,using off axis projection onto a transparent reflective diffuser displaysystem or other transparent display containing or coated with lightemitting particles 16 activated by a projector 13. The projector 13emits excitation light 15, including but not limited to UV or IR light.

In some examples, the projector 13 may be functionally coupled to acontroller (not illustrated in FIG. 2). The controller may include oneor more processors that, upon execution of software instructions (e.g.,locally stored by the controller within a tangible, non-transitorymemory or included within a received signal), causes the controller togenerate and transmit a control signal to the projector 13. Based on thereceived control signal, projector 13 may selectively emit and projectexcitation light 15 onto the transparent reflective diffuser displaysystem or the other transparent display, as described above.

UV sources include, but are not limited to, solid state lasers,semiconductor laser diodes, gas lasers, dye lasers, excimer lasers, andother appropriate UV light sources. The IR lasers include, but are notlimited to, solid-state lasers, semiconductor laser diodes and otherappropriate IR sources. Excitation beam intensities from the lightsource can be modulated to yield visible fluorescence of varyingchromaticity, intensity or gray scales. The excitation light is absorbedby light emitting particles that emit visible light to the retina of theviewer's eye. The intensity and placement of the output of one or moreprojectors, e.g., projector 13, is modulated to create one or moremoving apertures to appear in the field of view.

The light emitting particles 16 incorporated into the transparentdisplay 12 may be chromatic or achromatic. Light emitting particles maybe nano-particles or molecules, and thus smaller than the wavelength ofvisible light in order to eliminate light scattering and when activated,produce the less transparent to opaque area 18 ranging from 0.2 mm to 10mm in diameter, surrounding and defining a transparent aperture 14having a diameter ranging from 0.1 mm to 4 mm.

FIGS. 3A-3B, 4A-4D, and 5 illustrate additional exemplary embodiments ofdevices and methods for delivering visual information from an ocularfield of view to a retina using regional variation of the visualinformation to control sampling of the visual information by the retinalcells of an eye. This variation of visual information and sampling(e.g., V-VIS) is accomplished with the one or more of the devices andmethods illustrated in the following figures, but should not berestricted to or limited in scope to the embodiments shown.

FIG. 3A illustrates a partial cross section view and top view of a basiccomponent, defined herein as a carrier layer unit, of an exemplary V-VISdevice. A partial cross-section of the exemplary V-VIS device is shownin which two transparent layers 20A and 20B create a space 22 which ispartially filled with one or more active optical elements 24. In someexamples, transparent layers 20A and 20B can be flat or curved andcomposed of glass or plastic, and can include, but are not limited topolysulphones, polyetherimides, and/or other thermo-plastic materialshaving a refractive index of approximately 1.67 and thus no opticalpower. Further, the one or more active optical elements 24 be formedfrom a material having a refractive index of approximately 1.67, suchas, but not limited to, one of polymer light emitting diodes (PLED),bi-stable liquid crystals, surface stabilized ferroelectric liquidcrystals (SSFLF), transparent and color-tunable organic light-emittingdiodes (OLEDs), ferroelectric liquid crystal, super-twisted liquidcrystal, or a liquid crystal voltaic material.

The inside surface of each of transparent outer layers 20A and B, whichfaces the space 22, is lined with an optically transparent electricallyconductive layer 21A and 21B made of a conductive material, such as, butnot limited to, an indium tin oxide (ITO), a conductive organicmaterial, such as poly(3,4-ethylenedioxythiophene)poly(styrenesulfonate), and/or carbon nano-tubes. Further, theconductive material may also include traces of metals such, as silver oraluminum for increasing conductivity. The conductive layers 21A and 21Bcan be connected to a power 25 and drive box 26, which may be housed inone unit or divided into multiple units, and which may have an on/offswitch, power supply and drive software to apply a desired voltagethrough one or more areas of the conductive layer to the active opticalmaterial 24 which then changes its optical properties from transparentto varying degrees of opacity in response to the voltage. Multiplevariations in the color, and locations and size of areas of opacity andtransparency can be achieved by configuring some embodiments of theexemplary V-VIS devices with different patterns and densities of activeoptical material within the space 22 between the transparent outerlayers 20 A, B of the carrier layer and/or by configuring the pattern ofelectrical stimulation via the conductive layer.

In some embodiments of the exemplary V-VIS devices and methods, thecarrier layer can incorporate optical filters that block specific rangesof harmful wavelengths of light, including but not limited to blue andviolet wavelengths between 415 and 455 nm and/or UV wavelengths forprevention of retinal photo-damage.

In some embodiments of the exemplary V-VIS devices, the carrier layerincorporates a broad band anti-reflective (AR) coating that is appliedto the carrier layer to minimize ghosting. The AR coating can be eithera single layer MgF₂ or a multilayer coating. Multilayer coatings of avariety of materials and a variety of absolute and relative thicknessescan be used to achieve the AR function.

In some embodiments of the exemplary V-VIS methods and devices describedherein, each carrier layer unit has an arrangement of active opticalmaterial 24 surrounding an area 23 devoid of the active opticalmaterial. The aperture of these exemplary V-VIS devices and methods may,in some embodiments, be defined by an area without one or more activeoptical elements surrounded by an area in each carrier layer with theone or more active optical elements (e.g., the one or more activeoptical elements within each carrier layer become less transparent thanthe area of the aperture when electrified). The aperture can beconfigured with a diameter ranging from 0.1 mm to 4 mm, while thesurrounding area is configured to have a diameter ranging from 0.2 mm to10 mm. The degree of opacity of the aperture and/or surrounding area isdetermined by the density and placement of active optical material.

Multiple apertures can be formed within a single layer by virtue ofwhere active optical material is placed within that layer. In someembodiments, the size, location and opacity of the aperture and/orsurrounding area is determined by altering the pattern of electricalstimulation via the conductive layer (e.g., based on control signalsgenerated by a controller having a processor that executes locallystored or received software instructions). In some embodiments, the oneor more apertures in the carrier layer are defined as areas withoutactivation of the one or more active optical elements surrounded by anarea in the carrier layer characterized by activation of the one or moreactive optical elements. The position of the one or more apertures maybe determined by a selective application of electrical energy to one, ormore, of the carrier layers. The position of the one or more apertureschanges at a rate of between 50 hertz and 50 kilohertz. One position ofthe one or more apertures is coaxial with the center of the pupil, whilethe one or more other positions of the one or more apertures arenon-coaxial with the center of the pupil.

FIG. 3B is an illustration of vertical stacking of multiple carrierlayer units of FIG. 3A in order to create the moving aperture effect,according to some examples. A programmable controller 26 connected to apower source 25 sends electrical current either through a directconnection or remotely through a radio frequency antenna 27 to theactive optical material 24 in each of the carrier layer units 29. Insome examples, the programmable controller 26 may include one or moreprocessors that, upon execution of software instructions (e.g., locallystored by the controller within a tangible, non-transitory memory orincluded within a received signal), causes the programmable controller26 to route selectively the electrical current (e.g., as a controlsignal) to the active optical material 24 in each of the carrier layerunits 29 using any of the processes described herein.

Each carrier layer unit has an arrangement of active optical material 24surrounding an area 23 devoid of the active optical material. Theaperture of the exemplary V-VIS devices and methods is created by thearea without one or more active optical elements being surrounded by anarea in each layer with one or more active optical elements; the one ormore active optical elements within the carrier layer becomes lesstransparent than the area of the aperture when electrified, e.g., by thereceived electrical current. In some embodiments of the exemplary V-VISdevices, two or more transparent carrier layers are vertically stacked,such that the one or more active optical elements in each of the two ormore transparent carrier layers becomes less transparent than theaperture when electrified.

In some examples, as described herein, the one or more apertures can bedefined by at least one of an area without the one or more activeoptical elements being surrounded by an area in each carrier layer withthe one or more active optical elements. In other examples, the one ormore apertures can be defined by an area without activation of the oneor more active optical elements surrounded by an area in each carrierlayer with activation of the one or more active optical elements. Infurther examples, the spatial location of each of the one or moreapertures in each carrier layer can be displaced relative to each of theother apertures in each carrier layer. In some embodiments the locationand number of positions of the one or more apertures, the sequence ofpositions, and the interval between changes in positions may becustomized for a specific person or a specific condition, disease,injury or disorder.

FIGS. 4A-4D depict a cross section of an eye showing various exemplaryplacement locations for a V-VIS device anterior to a retina of the eye.In FIG. 4A, the eye has a cornea 30 overlying the iris 31. In someexamples, a V-VIS device, such as the exemplary V-VIS device illustratedin FIGS. 2 and 3, can be placed inside, or clipped to a spectacle lens33 or placed in one or more waveguides 34 connected to an eyeglass frame32. The frame 32 houses a power source 25 and programmable controller 26which is connected to the one or more carrier layers 29 in or attachedto the spectacle lens using an appropriate attachment method ormechanism. Each activated carrier layer produces one or more apertures23 as described previously, e.g., based on electrical currentselectively routed by the programmable controller 26 via the controlsignal. In some examples, the programmable controller 26 may receiveinput data, e.g., feedback from a sensor or a remotely accessible device(not illustrated in FIG. 4A), and may perform a calibration orconfiguration processes based on the received input.

FIG. 4A shows a single aperture in one position during a single samplinginterval. The chosen position sequence of the moving aperture and SIdetermine the sampling of light by the retina. The exemplary V-VISdevice of FIG. 4A can be configured to move optically an apertureanterior to a retina between one or more positions anterior to theretina that are non-coaxial with the center of the pupil and a positionanterior to the retina that is coaxial with the center of the pupil.

The transparent waveguide 34 shown in FIG. 4A can, for example, act as asee-through display. In some embodiments, the exemplary V-VIS devicesand methods described herein can include multiple waveguides arranged inat least one of vertically stacked in layers, adjacent to one another ina single layer, holographically multiplexed, or any combination thereof.Apertures and surrounding opaque areas such as those described in FIGS.2, 3A and 3B, can be projected through the waveguides to the retina.

In some embodiments, the see-through display of the exemplary V-VISdevices and methods described herein can be further configured todisplay at least one augmented reality image, at least one virtualreality image, or any combination thereof. In one example, theprogrammable controller 26 may maintain local data characterizing the atleast one virtual and/or augmented reality image within a tangible,non-transitory memory and, upon execution of software instructions, maygenerate a control signal that causes a V-VIS device to generate anddisplay the at least one virtual and/or augmented reality image, e.g.,on the transparent waveguide 34.

In other examples, the programmable controller 26 may be communicativelycoupled to a virtual-reality or augmented-reality (VR/AR) system ordevice across one or more communications networks, such as a short-rangecommunications network using Bluetooth™ communications protocols ornear-field communications (NFC) protocols. The programmable controller26 may receive data transmitted by the VR/AR system or device andresponsive to the data, generate the control signal that causes theV-VIS device to generate and display the at least one virtual and/oraugmented reality image, as described herein (not illustrated in FIG.4A).

An exemplary embodiment of the use of augmented reality is in the caseof a subject with loss of both vision and hearing, often co-morbiditiesin elderly patients, as well as in a number of inherited syndromes ordisorders such as Alport, Usher, Marshall, Stickler, Duane, Leber, andNorrie and in infectious diseases such as Cytomegalovirus and Rubella.One or more of the exemplary V-VIS devices, as described herein, may beconfigured to combine vision improving moving apertures with multipledirectional microphones 35 built into head-mounted or spectacle framesconnected to the VR/AR system or device. In some examples, and uponexecution of one or more application programs, the VR/AR system ordevice can perform operations that receive audio data captured by theone or more of the directional microphones 35. Based on the capturedaudio data, the VR/AR system or device can perform further operationsthat sense a source location of speech, convert the sensed speech totext of a preferred language, and display enlarged text (e.g., “Your momis calling”) 36 as an augmented reality image or layer on the waveguide34 within the field of view of the sight- and hearing-impaired subject.Further, in some embodiments, added directional cues are given by meansof one or more light emitting diodes placed around the perimeter of thefield of view (e.g., around a perimeter of waveguide 34) to indicate tothe hearing-impaired subject the direction from which the audible speechis produced. In some embodiments, one or more of the exemplary V-VISdevices described herein can include one or more microphones, and caninclude, or be in communication with, one or more processors orprocessing units that execute applications programs or softwareinstructions that convert an audible speech to a text in a preferredlanguage and to display the text within a field of view of a subjectusing the exemplary V-VIS devices. Further, and as described herein, oneor more of the exemplary V-VIS device may further comprise one or morelight emitting diodes placed around the perimeter of the field of viewto indicate the direction from which the audible speech is produced. Theapplication programs and the software instructions may include anApplication Programming Interface (API) to create visual alerts forincoming texts and phone calls, as well as other alerts andnotifications, and can convert speech from the telephone to viewabletext.

In some embodiments, one or more of the exemplary V-VIS device can becombined with an eye tracking or gaze interactive assistive technology,examples of which include, but are not limited to, technologiesavailable from Tobii Dynavox (Pittsburgh, Pa.) for subjects with speechand/or motor impairments. As the exemplary V-VIS devices and methods canimprove a visually impaired subject's ability to see, eye tracking orgaze interactive assistive technology allows subjects who also havespeech or motor disability to better focus their gaze on words, lettersand commands, which results in improved eye tracking and infrared reflexreadings from the corneal surface of their eyes, allowing them tocommunicate, regain personal independence, learn and interact withothers and with computers, write emails, access social networking sites,acquire new skills and promote creativity, thereby increasing health andhappiness.

In another exemplary embodiment, the head mounted or spectacle frames(e.g., as connected by Bluetooth™ to the processor described herein) canbe combined with cameras directed peripherally in order to treatsubjects with partial loss of the normal field of view, such as in, forexample, subjects with hemianopsia, quadrantanopia or unilateral loss oftemporal visual fields. Using AR techniques concurrent with theintermittent V-VIS display of the current field of view, light carryinginformation from the lost part of the total field of view is deliveredto the remaining functional parts of the retina-brain complex forinterpretation, integration and viewing. The intermittency of V-VISprevents confusion and distraction that would result if the missingparts of the field of view were constantly displayed in a conventionalpicture-within-picture technique.

In some embodiments, one or more of the exemplary V-VIS devices can becombined with a concurrent display of augmented reality content (e.g.,on a corresponding waveguide, etc.), wherein the use of augmentedreality together with V-VIS captures light from a field of view largerthan the field of view of a subject's eye, fellow eye or both eyes anddelivers the light to the retina. The visual field of an eye normallyextends more than 90° temporally, 60° nasally and superiorly, and about70° inferiorly. In some embodiments, the exemplary V-VIS devices andmethods described herein can expand the field of view of a subject'seye, fellow eye or both eyes for a total field of view that can beconfigured to be fixed or variable and to encompass any chosen number ofdegrees up to 360 degrees around the subject's eye, fellow eye or botheyes. In further embodiments, the exemplary processor described hereincan be combined with cameras directed peripheral to and/or above and/orbelow and/or behind an eye, fellow eye or both eyes. In additionalembodiments, the one or more of the V-VIS devices can be combined with aconcurrent augmented reality display, wherein the use of augmentedreality together with V-VIS captures light from a field of view largerthan the field of view of a V-VIS device alone or an AR device alone toprovide the subject with an expanded field of view. In some embodiments,the combination of the V-VIS and AR devices comprises 3D detectionand/or high speed tracking. In some embodiments of the devices andmethods that are configured for the use of V-VIS combined with AR, lightcollimated by V-VIS apertures can be delivered to a retina from a fieldup to 360 degrees around an eye or both eyes of a subject. In someembodiments, one or more of the exemplary V-VIS devices can be furtherconfigured with one or more cameras and software to capture light fromat least one of peripheral to, above, below and behind an eye, a felloweye or both eyes of a subject and deliver the light to the retina of theeye, the fellow eye or both eyes of the subject.

FIG. 4B shows two different embodiments of an exemplary V-VIS devicethat includes a contact lens 40 overlying a cornea 30 and iris 31. Thecontact lens 40 is corneal or scleral, or any combination thereof. Oneexemplary embodiment utilizes off-axis projection, as described in FIG.2. For example, a projector 13 is mounted external to a contact lens 40,which contains light emitting particles. Excitation light 15 from theprojector creates the moving aperture effect within or on the contactlens surface using any of the exemplary processes described herein, suchas those described in FIG. 2.

In another embodiment, also shown in FIG. 4B, the contact lens 40 hasone or more carrier layers 29, as described in FIG. 3A and 3B, each ofwhich include active optical material 24 defining one or more apertures23. One or more antennas, such as antenna 27, receive signals thatinclude instructions on the sequence, duration of, and interval betweenactivation of the apertures. FIG. 4B shows a moving aperture at oneposition during a single sampling period of time.

In one example, the received signals may include radio frequencysignals, and the antenna 27 may include a radio frequency antennacapable of receiving the radio frequency signals. The disclosedexemplary embodiments are not limited to radio frequency signals andantennas, and in other examples, the antenna 27 may be capable ofreceiving transmitted signals formatted in accordance with anyadditional, or alternate, communications protocols, such as thosedescribed herein.

Further, in some examples, the antenna 27 may receive the signals from acorresponding transmitter unit included within (or disposed on)eyeglasses worn by the subject, included within a mobile device operatedby the subject or by a physician, or from any other appropriate deviceor system, e.g., across any of the communications networks describedherein. The software instructions may, for instance, be generated orspecified by the physician, and stored within one or more tangible,non-transitory memories of the eyeglasses, the mobile device, or theother appropriate device or system.

In FIG. 4C, the exemplary V-VIS device includes an intra-corneal inlay45, which includes one or more built-in antennas, such as the antenna27, capable of receiving transmitted signals. Examples of thetransmitted signals include, but not limited to, radio frequency signalsor signals formatted in accordance with any additional, or alternate,communications protocols, such as those described herein.

The corneal inlay is placed within the cornea 30, which overlies theiris 31. When activated (e.g., based on signals received by the antenna27), the active optical material 24 in the one or more transparentcarrier layers 29 inside the corneal inlay 45 form one or more movingapertures 23. FIG. 4C shows a moving aperture at one position during asingle sampling period of time.

In FIG. 4D, the exemplary V-VIS device comprises an intraocular implant46, which replaces a human crystalline lens and is usually placed insidethe capsular bag 47 of the eye behind the iris 31, although it can beplaced above the bag or above the iris 31 in some embodiments. Theexemplary V-VIS device can include an intraocular device, an intraocularlens (IOL), an intraocular lens accessory device (IOLAD), or anycombination thereof for insertion in a phakic, aphakic or pseudophakiceye, including at least one of an anterior chamber, sulcus-fixated,iris-fixated, capsular bag fixated or transcleral sutured IOL or IOLAD.When activated (e.g., based on signals received by one or more built-inantennas, such as the antenna 27), the active optical material 24 in theone or more transparent carrier layers 29 inside the implant form one ormore moving apertures 23. FIG. 4D shows multiple moving apertures at oneposition during a single sampling period of time. The exemplary V-VISdevice moves the one or more apertures by directing an electricalcurrent (e.g., derived from signals received by the antenna 27) througheach of one or more transparent carrier layers containing one or moreactive optical elements.

In some embodiments, a refractive error of an eye can be corrected byincorporating the appropriate lens for correction of ametropia into oneor more of the exemplary V-VIS devices described herein, such as, butnot limited to, spectacles, contact lens, corneal inlay, or intraocularlens.

In an exemplary embodiment, the power source for each carrier layerinside of a contact lens, corneal inlay or intraocular implant may beradio frequency (RF) transmission aided by rechargeable solarmicro-batteries which may be built into corresponding ones of theexemplary V-VIS devices. For example, a micron size solar poweredmicro-battery, which provides added power to extend the range of radiofrequency (RF) power sources to its RF antennas, can be incorporatedinto one or more of these exemplary V-VIS devices.

FIG. 5 shows six different moments in time (e.g., moments A-F), withfive possible aperture positions. As illustrated in FIG. 5, atransparent aperture 51A in the position coaxial with the center of thepupil alternates during different sampling cycles with an opaqueaperture 50D in the position coaxial with the center of the pupil ineach lens. Further, in FIG. 5, an exemplary V-VIS device includes a pairof spectacles configured to treat a subject with amblyopia. Theexemplary V-VIS device may be built into the lenses 33 of spectacleframes 32.

In some embodiments of an exemplary V-VIS device that treats amblyopia,the entire central view in front of an eye is obstructed (e.g., 50A and50D) for a least one sampling cycle, while a central transparentaperture coaxial with the center of the pupil appears simultaneously infront of the fellow eye (e.g., 51A and 51D). The completely obstructedcentral view alternates between the two eyes after every sampling cycleor after every several sampling cycles. At the other sampling intervals(SIs) during each sampling cycle, transparent apertures appear in frontof both eyes in positions that are non-coaxial with the center of thepupil, e.g., in 52B, 52C, 52E, and 52F. The apertures and surroundingopaque areas can be colored or opaque to desired densities from 10%to100% opaque, depending on the density and type of optically activematerial placed in the one or more carrier layers of the exemplary V-VISdevice. The aperture positions change at a pre-determined sampling rate(SR) between 50 hertz and 50 kilohertz. Depending upon the severity andtype of amblyopia, the presentation duration, the color and/or thedensity of the central opacity, e.g., 50A and 50D can be adjusted tolast longer or to be denser to strengthen and/or improve visual pathwaysand perception of the amblyopic eye or eyes.

Some embodiments of the exemplary V-VIS devices and methods, asdescribed herein, overcome limitations of conventional therapies foramblyopia, including, but not limited to, inadequate improvement ofvisual function because of lack of intensive bilateral stimulation ofvisual pathways and/or obstruction of peripheral fields and/orcompliance problems. The visual periphery has been documented to berelatively spared from vision loss in amblyopia. Conventional treatmentfor amblyopia, unlike some embodiments of these exemplary V-VIS devicesand methods, decreases the number of spatial samples, particularly inthe periphery, available for accurate integration of visual informationand often results in loss of binocularity and/or inability to improvebinocularity during treatment, as well as impairment of the ability tointegrate peripheral visual field information in the visual cortex.Unlike conventional shutter or flicker glasses for amblyopia that blockthe peripheral view, some embodiments of the exemplary V-VIS devices foramblyopia preserve the visual representations of the peripheral visualfield, because the peripheral view is never obstructed. Conventionalvisual training for amblyopia using conventional electronic devices withvirtual reality (VR) displays cannot be used during normal activities,are used only for short training sessions and do not improve visionwhile the visually impaired subject is viewing objects in a naturalscene or during normal visual tasks. Some embodiments of V-VIS therapyfor amblyopia (e.g., which utilize one or more of the exemplary V-VISdevices and methods described herein), unlike conventional amblyopiatreatments, allow for intensive binocular stimulation, which engagesplasticity mechanisms in the entire visual pathway of FIG. 1. Some eyeswith amblyopia also have dystrophic retinal cells. Unlike conventionalglasses for amblyopia, some embodiments of the exemplary V-VIS devicesfor amblyopia can be configured to increase or decrease stimulation ofdifferent retinal areas because of the moving apertures, as well as thecombination of AR or VR with one or more of the exemplary V-VIS methodsand device in some configurations. Beneficial stimulation for amblyopiamay be enhanced in some embodiments of the exemplary V-VIS methods anddevices by adding red, green, or blue color to the central opaque regionin order to isolate the excitation of individual sets of conephotoreceptors.

One or more of the extraocular V-VIS devices shown in the precedingfigures, such as eyeglasses, an eyeglass accessory device, heads updisplay, visor, contact lens and a viewing screen, including, but notlimited to, a remotely accessible-television, computer or mobile device,may be utilized for at least one of screening for V-VIS effects,customization of V-VIS, calibration of V-VIS, vision measurement, visionmonitoring or any combination thereof. In one embodiment of theexemplary V-VIS methods and devices described herein, the SR would beset at rate too fast to allow perception and gradually slowed until thesubject could first perceive a visual target. In some embodiments, thisSR not only would allow for customization of the V-VIS treatment basedon patient-provided feedback but also would define a functionalmeasurement of the person's visual processing ability, which would varybetween subjects, depending upon their age and underlying ophthalmic orneurologic disorders. Thus, the V-VIS devices and methods could beutilized diagnostically.

Another embodiment of the exemplary V-VIS methods and devices isdepicted in FIG. 6. In FIG. 6, the viewing screen of one or more of theexemplary V-VIS devices described herein (e.g., a remotelyaccessible-television, computer or mobile device, etc.) may present, toa subject, a display 61 that includes letters, numbers and/or objects ofvarying locations, sizes and/or contrast delivered to the retina by oneor more moving revealing apertures. By way of example, display 61 mayinclude a portion of an eye chart, which may be selectively and variablyobscured by the moving apertures.

In some instances, the subject may establish a channel of communicationswith a testing, diagnostic, monitoring, or testing facility bytelephone, (e.g., by dialing a toll-free number), by instant messaging,or through other internet-based or electronic communications mechanisms.Referring to FIG. 6, the subject may be directed to fixate on a targetcoaxial with the center of the pupil (e.g., target 62 of FIG. 6) on anotherwise darkened display 61 (e.g., by contrast). At least onerevealing aperture 63 is moved at a rate between 50 hertz and 50kilohertz between one or more positions 64 anterior to the retina on thedisplay that are non-coaxial with the center of the pupil (e.g.,revealing characters “Z” and “N” within the eye chart) and a position 65anterior to the retina on the display 61 that is coaxial with the centerof the pupil (e.g., revealing character “H” of the eye chart). Asillustrated in FIG. 6, the at least one revealing aperture 63 (e.g., atpositions 64 and 65) delivers to the retina a portion of the display61's total field of view otherwise obscured by the darkened screen andthe display 61's total field of view includes test images.

The subject's visual perception of the test images is measured andmonitored by the subject's responses using recording and data collectionmethods known to those skilled in the art. For example, the subject mayprovide information identifying each of the letters or numbers visiblewithin display 61 to the facility across the established channel ofcommunications, and a computing system maintained by the facility mayreceive the provided information (e.g., through one or more programmaticinterfaces or based on input provided by an agent or employee of thefacility).

The computer may, in some instances, execute stored softwareinstructions that generate (and store) a record of the identifiedletters and numbers, and that determine one or more letters or numbersmissed by the subject based on a comparison between the identifiedrecord and information characterizing the movement and positioning ofthe at least one revealing aperture relative to the text images. Basedon the determination, the computer may perform operations that generatea map of the of the subject's full visual field using any of theexemplary V-VIS methods described herein. For example, the generated mapmay identify a position or a size of a scotoma exhibited by the subjectand additionally, or alternatively, an area of metamorphopsia exhibitedby the subject. Further, variations of the size of the presented lettersor numbers may facilitate a determination of a potential visual acuityof the subject based on the generated map. Some embodiments of theexemplary V-VIS devices and methods described herein measure and monitorvisual perception and/or vision more conveniently and/or more accuratelythan conventional devices and methods.

One or more of the exemplary V-VIS devices and methods, as describedherein, include or utilize a light control device to move one or moreapertures anterior to a retina between one or more positions anterior tothe retina that are non-coaxial with a center of a pupil and a positionanterior to the retina that is coaxial with the center of the pupil. Theone or more apertures may, for example, be moved at a rate between 50hertz and 50 kilohertz, thereby to produce a regional variation ofvisual information and sampling (V-VIS) of the ocular field of view.Further, the phrase “anterior to the retina” includes one ofextraocular, intracorneal or intraocular placement, and the device canelectro-optically move the one or more apertures through one or moresee-through displays placed anterior to the retina.

In further embodiments, the light control device can be utilized for atleast one of V-VIS by a subject, for at least one of screening for useof V-VIS, customization of V-VIS, calibration of V-VIS, V-VIS visionmeasurement, V-VIS vision monitoring, or any combination thereof. Insome instances, the V-VIS device can be configured to produce at leastone of an improvement of vision in an eye or both eyes of a subject, astabilization of vision in an eye or both eyes of a subject, acorrection of an ophthalmic or neurologic condition, an amelioration ofa visual symptom in an eye or both eyes of a subject with an ophthalmicor neurologic condition, disease, injury or disorder, a reduction of arate of vision loss compared to an untreated control group in an eye orboth eyes of a subject with vision loss from an ophthalmic or neurologiccondition, disease, injury or disorder, a reduction of a rate ofprogression of an ophthalmic condition, disease or disorder compared toan untreated control group in an eye or both eyes of a subject with anophthalmic condition, disease, or disorder, a vision measurement of aneye or both eyes of a subject, a vision monitoring of an eye or botheyes of a subject, or any combination thereof.

In some embodiments, one or more of the exemplary V-VIS devices andmethods combine V-VIS teachings with certain ophthalmic and neurologictreatments. Some therapeutic embodiments include treating an eye with amethod comprising utilization of a V-VIS device, together withadministration of another therapy for an ophthalmic or a neurologiccondition, disease, injury or disorder. The V-VIS device can beconfigured to move optically one or more apertures anterior to a retinaof an eye between one or more positions anterior to the retina that arenon-coaxial with a center of a pupil and an position anterior to theretina that is coaxial with the center of the pupil (e.g., in accordancewith any of the processes described herein), and the one or moreapertures are moved at a rate between 50 hertz and 50 kilohertz. In someembodiments, one or more of the exemplary V-VIS devices and methods canbe combined with other ophthalmic and neurologic treatments thatinclude, but are not limited to: pharmacological and/or nutritionalsupplemental and/or laser and/or radiation and/or retinal replacementand/or stem cell transplantation and/or epigenetic and/or genetic and/oroptogenetic and/or retinal prosthetic and/or other therapy (hereafterother therapies) in order to improve treatment of ophthalmic conditions,diseases, injuries and disorders, including, but not limited to, maculardegeneration and/or diabetic retinopathy and/or glaucoma and/or axialmyopia and/or other neovascular and/or atrophic and/or inflammatoryand/or inherited and/or nutritional and/or age-related retinalconditions, diseases, injuries or disorders (hereinafter “ophthalmicdiseases”) and/or neurologic diseases, disorders or conditions(hereinafter “neurologic diseases). Certain of the exemplary V-VISdevices and methods described herein overcome drawbacks and deficienciesof conventional therapies by introducing different mechanisms of visualsampling and/or visual processing and/or visual perception and/orretinal repair processes and/or neural repair processes associated withophthalmic and/or neurologic diseases. Further, certain of the exemplaryV-VIS devices and methods overcome drawbacks and deficiencies of othertherapies by synergistically combining them with V-VIS to improve visualand/or anatomic outcomes, which also improves patient compliance withother therapy. In combination therapy with V-VIS, other therapy can beadministered before, during or after V-VIS. In some embodiments ofcombination therapy, V-VIS treatment is administered either beforenon-V-VIS therapy or at some time following initiation of non-V-VIStherapy.

In some embodiments, V-VIS treatment can be combined with othertherapies for ophthalmic and neurologic diseases, including but notlimited to laser therapies, including but not limited tophotobiomodulation, laser photocoagulation, laser photodynamic therapy,subthreshold micropulse laser therapy, glaucoma laser therapy,(including, but not limited to, laser trabeculoplasty andcyclophotocoagulation), glaucoma filtration surgery (including, but notlimited to, trabeculectomy, microtrabeculectomy, internal or externaltube shunt implantation, suprachoroidal shunt implantation), visioncorrection (including, but not limited to, refractive surgery, laservision correction and genetic therapy), optic nerve surgery(including,but not limited to, decompression and repair surgery), retinalprostheses, stein cell transplantation, and radiation therapy (includingbut not limited to focal intraocular strontium 90 beta radiation).

Some embodiments include treating an eye with V-VIS (e.g., based on autilization of one or more of the exemplary V-VIS devices and methodsdescribed herein) in combination with administering at a time prior toV-VIS, during V-VIS, after V-VIS, or any combination thereof, at leastone of a genetic, epigenetic, optogenetic, retinal replacement or stemcell therapy for treating an ophthalmic disorder. In furtherembodiments, a therapeutic or treatment method (e.g., a “combination”method) for treating an eye can include a utilization of a V-VIS device,together with administration, at a time prior to V-VIS, during V-VIS,after V-VIS or any combination thereof, of at least one of a genetic,epigenetic, optogenetic, retinal replacement or stem cell therapy fortreating an ophthalmic or neurologic disease. As described herein, thedevice can be configured to move optically one or more aperturesanterior to a retina of an eye between one or more positions anterior tothe retina that are non-coaxial with a center of a pupil and an areaanterior to the retina that is coaxial with the center of the pupil(e.g., in accordance with any of the processes described herein), andthe one or more apertures are moved at a rate between 50 hertz and 50kilohertz.

In some embodiments of combination therapy, V-VIS treatment improvesand/or facilitates and/or expedites recovery and/or restoration ofvisual functioning, including, but not limited to, at least one ofneural connectivity, neural integration, visual sampling or visualperception after genetic, epigenetic, optogenetic, retinal replacementor stem cell therapy. In some embodiments, the combination of V-VIS withretinal replacement and/or stem cell therapy, overcomes limitations ofretinal replacement and/or stem cell therapy, including, but not limitedto incorrect or inadequate targeted delivery of stem cells or otherretinal cells. In some embodiments, treatment for retinal dystrophiesand/or degenerations combined with V-VIS treatment, unlike retinalprostheses and optogenetic therapy alone, overcomes limitations indystrophic retinas, including, but not limited to, aberrant remodelingof intraretinal connections and pathological spontaneous hyperactivityin dystrophic retinas. In some embodiments, treatment for retinaldystrophies and/or degenerations combined with V-VIS treatment overcomeslimitations of retinal prostheses and optogenetic therapy in dystrophicretinas, including, but not limited to, central scotoma creation,because of displacement of retinal ganglion cells from the fovea, andcolor encoding difficulties, because of insufficient knowledge of whichganglion cells encode which color channels.

In further embodiments, one or more of the exemplary V-VIS devices andmethods, as described herein, can be combined with anti-angiogenesistherapy for treating or ameliorating a symptom of a neovascularophthalmic condition, disease, injury or disorder, including, but notlimited to, a macular degeneration, a choroidal neovascularization and adiabetic retinopathy. Some embodiments include treating an eye withV-VIS (e.g., utilizing one or more of the exemplary V-VIS devices andmethods described herein) in combination with administering, at a timeprior to V-VIS, during V-VIS, after V-VIS or any combination thereof, atherapeutically effective amount of an anti-angiogenesis agent that isadministered via intravitreal injections, orally, topically,intraretinally, via implants or via iontophoresis. As used herein, theterm “ameliorating” or “treating” or “compensating for” means that theclinical signs and/or symptoms associated with an ocular disorder (e.g.,macular degeneration) are lessened as result of the actions performed.The signs or symptoms to be monitored will be characteristic of theocular disorder and will be well known to physicians skilled in the art,as well the methods for monitoring the signs, symptoms and conditions.Combination therapy utilizing V-VIS together with anti-angiogenesistherapy would be advantageous over anti-angiogenesis alone or V-VISalone, because the combination therapy would further improve functionalvision, further stabilize functional vision, decrease treatment burdenand/or improve patient compliance.

Some embodiments described herein provide a method of ameliorating ortreating a neovascular ophthalmic condition, disease, injury or disorderby treating an eye with V-VIS (e.g., utilizing one or more of theexemplary V-VIS devices and methods) in combination with administering atherapeutically effective amount of an anti-angiogenesis agent,including but not limited to a vascular endothelial growth factor (VEGF)antagonist (an inhibitor of VEGF activity), including, but not limitedto, aflibercept, ranibizumab, bevacizumab and brolucizumab.

Some embodiments described herein provide a method of ameliorating ortreating a neovascular ophthalmic condition, disease, injury or disorderby treating an eye with V-VIS (e.g., utilizing one or more of theexemplary V-VIS devices and methods) in combination with administering atherapeutically effective amount of an anti-angiogenesis agent,including, but not limited to, a platelet-derived growth factor (PDGF)antagonist, including, but not limited to, volociximab and P200.

Some embodiments also provide a method of treating or ameliorating aneovascular ophthalmic condition, disease, injury or disorder bytreating an eye with V-VIS (e.g., utilizing one or more of the exemplaryV-VIS devices and methods) in combination with administering atherapeutically effective amount of an anti-angiogenesis agent,including, but not limited to, an angiopoietin antagonist including, butnot limited to, or an angiopoietin-2 antagonist, including but notlimited to, RG7716.

Some embodiments described herein provide a method of ameliorating ortreating a neovascular ophthalmic condition, disease, injury or disorderby treating an eye with V-VIS (e.g., utilizing one or more of theexemplary V-VIS devices and methods) in combination with administering atherapeutically effective amount of an anti-angiogenesis agent,including, but not limited to, an endoglin antagonist, including, butnot limited to, carotuximab.

Some embodiments described herein provide a method of ameliorating ortreating a neovascular ophthalmic condition, disease, injury or disorderby treating an eye with V-VIS (e.g., utilizing one or more of theexemplary V-VIS devices and methods) in combination with administering atherapeutically effective amount of an anti-angiogenesis agent,including, but not limited to, an inhibitor of phosphorylation of VEGFand PDGF receptors, including but not limited to a tyrosine kinaseinhibitor, including, but not limited to, vetalanib or pazopanibor.

Some embodiments described herein provide a method of ameliorating ortreating a neovascular ophthalmic condition, disease, injury or disorderby treating an eye with V-VIS (e.g., utilizing one or more of theexemplary V-VIS devices and methods) in combination with administering atherapeutically effective amount of an anti-angiogenesis agent,including, but not limited to, an integrin antagonist, including, butnot limited to, an anti-integrin peptide, an inhibitor of alpha5beta1integrin activity and an oligopeptide binding to integrin receptorsites, including, but not limited to, luminate.

Some embodiments described herein provide a method of ameliorating ortreating a neovascular ophthalmic condition, disease, injury or disorderby treating an eye with V-VIS (e.g., utilizing one or more of theexemplary V-VIS devices and methods) in combination with administering,at a time prior to V-VIS, during V-VIS, after V-VIS or any combinationthereof, a therapeutically effective amount of two or moreanti-angiogenesis agents, including but not limited to, any VEGFantagonist, any PDGF antagonist, any angiopoietin antagonist, anyendoglin antagonist, and any integrin antagonist, wherein the two ormore anti-angiogenesis agents are delivered together or sequentially.

In other embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, a neovascular ophthalmic diseaseand/or wet macular degeneration, and/or diabetic retinopathy, in asubject includes treatment with V-VIS (e.g., utilizing one or more ofthe exemplary V-VIS devices and methods) in combination withadministering a therapeutically effective amount of an anti-inflammatoryagent, including, but not limited to, fluocinolone acetonide, whereinthe anti-inflammatory agent is administered via intravitreal injections,orally, topically, intraretinally, via implants or via iontophoresis.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, geographic atrophy and/or drymacular degeneration, in a subject includes treatment with V-VIS (e.g.,utilizing one or more of the exemplary V-VIS devices and methods) incombination with administering via intravitreal injections, orally,topically, intraretinally, via implants or via iontophoresis. atherapeutically effective amount of an inhibitor of complement,including, but not limited to, an inhibitor of complement 3 or 5activity, including, but not limited to, avacincaptad pegol, LEG316,POT¬4, eculizumab, JPE-1375, ARC1905, or a therapeutically effectiveamount of an anti-inflammatory agent, including, but not limited to, anantibiotic in the tetracycline class, including, but not limited to,doxycycline, or a therapeutically effective amount an immunomodulatingagent, including, but not limited to, a T helper 2 inducer, including,but not limited to, glatiramer acetate.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, geographic atrophy and/or drymacular degeneration in a subject, includes treatment with V-VIS (e.g.,utilizing one or more of the exemplary V-VIS devices and methods) incombination with administering a therapeutically effective amount ofOT551, or any other downregulator of overexpression of the proteincomplex nuclear factor (NF)¬B or any other antioxidant, or combinationof antioxidants, including but not limited to combinations of vitamin C,vitamin E, beta-carotene or lutein and zeaxanthin, and omega-3 fattyacids as in for, example, the Age-Related Eye Disease Study (AREDS) andAREDS 2 studies.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, geographic atrophy and/or drymacular degeneration in a subject, includes treatment with V-VIS (e.g.,utilizing one or more of the exemplary V-VIS devices and methods) incombination with administering a therapeutically effective amountnicotinamide adenine dinucleotide (NAD) or any precursors of NAD,including but not limited nicotinamide riboside or nicotinamidemononucleotide.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, geographic atrophy and/or drymacular degeneration in a subject, including treatment with V-VIS (e.g.,utilizing one or more of the exemplary V-VIS devices and methods) incombination with administering a therapeutically effective amount of atrophic factor including, but not limited to, pigment epithelium-derivedfactor (PEDF), fibroblast growth factors (FGFs) and lensepithelium-derived growth factor (LEDGF).

Some embodiments include treating an eye with V-VIS (e.g., utilizing oneor more of the exemplary V-VIS devices and methods) in combination withadministering topically, intraretinally, via intravitreal injections,via implants or via iontophoresis, at a time prior to V-VIS, duringV-VIS, after V-VIS, or any combination thereof, a therapeuticallyeffective amount of at least one of the following for treating anophthalmic or neurologic condition, disease, injury or disorder,including, but not limited to, a glaucoma, a macular degeneration, anoptic nerve atrophy, an autoimmune neuro-degenerative disorder or acerebrovascular accident: i. an intraocular pressure-lowering agent,including but not limited to a miotic, an alpha or alpha/beta adrenergicagonist, a beta-blocker, a Ca2+ channel blocker, a carbonic anhydraseinhibitor, a cholinesterase inhibitor, a prostaglandin agonist, aprostaglandin, a prostamide, a cannabinoid, or any combination thereof;ii. a retinal cell- or cortical cell-neuroprotective orneuroregenerative agent, including but not limited to a rho-kinaseinhibitor, an adenosine receptor agonist, a glutamate antagonist, aneurotrophic factor or a neurotrophic factor regulator; or iii. anycombination thereof. Such combination therapy would further improvefunctional vision, further stabilize functional vision, decreasetreatment burden and/or improve patient compliance.

In some embodiments, a method of treating or ameliorating an ophthalmicor neurologic disease, such as, but not limited to, geographic atrophyand/or dry macular degeneration and/or glaucoma in a subject, includestreatment with V-VIS (e.g., utilizing one or more of the exemplary V-VISdevices and methods) in combination with administering a therapeuticallyeffective amount of ciliary neurotrophic factor (CNTF) or any otherneurotrophic factors or any other inhibitors of photoreceptor apoptosis.

In some embodiments, a method of treating or ameliorating an ophthalmicor neurologic disease, such as, but not limited to, geographic atrophyand/or dry macular degeneration and/or glaucoma in a subject comprisingtreatment with V-VIS (e.g., utilizing one or more of the exemplary V-VISdevices and methods) in combination with administering a therapeuticallyeffective amount of a neuroprotective agent, including, but not limited,to brimodinine.

In some embodiments, a method of treating or ameliorating an ophthalmicor neurologic disease, such as, but not limited to, geographic atrophyand/or dry macular degeneration in a subject comprising treatment withV-VIS (e.g., utilizing one or more of the exemplary V-VIS devices andmethods) in combination with administering a therapeutically effectiveamount of a Fas inhibitor or other agent designed to protect retinalcells from cell death.

In some embodiments, a method of treating or ameliorating an ophthalmicor neurologic disease, such as, but not limited to, geographic atrophyand/or dry macular degeneration and/or neovascular macular degenerationand/or glaucoma in a subject, includes treatment with V-VIS (e.g.,utilizing one or more of the exemplary V-VIS devices and methods) incombination with administering a therapeutically effective amount of astatin, including, but not limited to, atorvastin, lovastation,rosuvastatin, fluvastatin or simvastatin.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, glaucoma or ocular hypertension,in a subject, includes treatment with V-VIS (e.g., utilizing one or moreof the exemplary V-VIS devices and methods) in combination withadministering a therapeutically effective amount of an intraocularpressure (IOP)—lowering agent, including, but not limited to, a miotic,an alpha or alpha/beta adrenergic agonist, a beta-blocker, a Ca²+channel blocker, a carbonic anhydrase inhibitor, cholinesteraseinhibitor, a prostaglandin agonist, a prostaglandin, a prostamide, acannabinoid, and combinations thereof.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, glaucoma in a subject, includestreatment with V-VIS (e.g., utilizing one or more of the exemplary V-VISdevices and methods) in combination with administering a therapeuticallyeffective amount of a pharmacological agent decreasing retinal ganglioncell dysfunction and/or pathology, related to ischemia orexcitotoxicity.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, including, but not limited to, glaucoma in a subject, includestreatment with V-VIS (e.g., utilizing one or more of the exemplary V-VISdevices and methods) in combination with administering a therapeuticallyeffective amount of a pharmacological agent decreasing excessiveexcitatory amino acid (EAA) stimulation, including, but not limited to,a glutamate antagonist and/or any combination of a glutamate antagonistand at least one IOL-lowering agent.

In some embodiments, a method of treating or ameliorating an ophthalmicdisease, such as, but not limited to, glaucoma in a subject, includestreatment with V-VIS (e.g., utilizing one or more of the exemplary V-VISdevices and methods) in combination with administering a therapeuticallyeffective amount of a pharmacological agent providing neuroprotectionand/or neuroregeneration of retinal ganglion cells, including but notlimited to a rho-kinase (ROCK) inhibitor or an adenosine receptoragonist.

1-19. (canceled)
 20. A light control device, comprising: one or morelayers disposed anterior to a retina of an eye; one or more opticallyactive materials disposed on a surface of, or within, the one or morelayers; and a controller coupled to a power source, the controller beingcoupled electrically to the one or more optically active materials viaan electrically conductive layer and being configured to generate androute control signals to the one or more optically active materials inaccordance with a temporal sequence; wherein anterior to the retinacomprises one of extraocular, intracorneal or intraocular placement;wherein, upon receipt of the control signals, the one or more opticallyactive materials produce one or more areas on the surface of, or within,the one or more layers having an altered transparency, the one or moreareas defining one or more apertures that include transparent areas; andwherein the one or more apertures appear optically at spatiallyseparated or overlapping positions on the surface of, or within, the oneor more layers in accordance with the temporal sequence, at least one ofthe spatially separated or overlapping positions being non-coaxial witha center of a pupil of the eye; and wherein the one or more aperturesgenerate a moving aperture effect that samples and delivers to theretina environmental light from an ocular field of view at a samplingrate between 50 hertz and 50 kilohertz.
 21. The light control device ofclaim 20, further configured to deliver approximately collimated lightfrom the ocular field of view through at least one of the one or moreapertures.
 22. The light control device of claim 20, further comprisinga lens.
 23. The light control device of claim 20, further configured togenerate and route control signals to the one or more optically activematerials to sample and deliver environmental light through at least oneof the one or more apertures to a viable cell-containing portion of adiseased or damaged retina.
 24. The light control device of claim 20,further configured to generate and route control signals to the one ormore optically active materials to sample and deliver environmentallight through at least one of the one or more apertures to a geneticallyaltered portion of the retina.
 25. The light control device of claim 20,further configured to generate and route control signals to the one ormore optically active materials to sample and deliver environmentallight through at least one of the one or more apertures to a portion ofthe retina that includes at least one of a retinal transplant, animplanted retinal cell, an implanted stem cell, or an implantedprosthesis.
 26. A light control device, comprising: a projection unit;one or more layers disposed anterior to a retina of an eye; opticallyactive material disposed on a surface of, or within, the one or morelayers; and a controller coupled to a power source, the controller beingcoupled electrically to the projection unit and being configured togenerate and route control signals to the projection unit in accordancewith a temporal sequence; wherein anterior to the retina comprises oneof extraocular, intracorneal, or intraocular placement; wherein, uponreceipt of each of the control signals, the projection unit projectsexcitation light onto a portion of the one or more layers, the opticallyactive material disposed on the surface of, or within, the portion ofthe one or more layers absorbing the excitation light and producing oneor more areas having an altered transparency, the one or more areasdefining one or more apertures that include transparent areas; andwherein the one or more apertures appear optically at spatiallyseparated or overlapping positions within or on the one or more layersin accordance with the temporal sequence, at least one of the spatiallyseparated or overlapping positions being non-coaxial with a center of apupil of the eye; wherein the one or more apertures generate a movingaperture effect that samples and delivers to the retina environmentallight from an ocular field of view at a sampling rate between 50 hertzand 50 kilohertz.
 27. The light control device of claim 26, furtherconfigured to deliver approximately collimated light from the ocularfield of view through at least one of the one or more apertures.
 28. Thelight control device of claim 26, further comprising a lens.
 29. Thelight control device of claim 26, further configured to generate androute control signals to the projection unit to sample and deliverenvironmental light through at least one of the one or more apertures toa viable cell-containing portion of a diseased or damaged retina. 30.The light control device of claim 26, further configured to generate androute control signals to the projection unit to sample and deliverenvironmental light through at least one of the one or more apertures toa genetically altered portion of the retina.
 31. The light controldevice of claim 26, further configured to generate and route controlsignals to the projection unit to sample and deliver environmental lightthrough at least one of the one or more apertures to a portion of theretina that includes at least one of a retinal transplant, an implantedretinal cell, an implanted stem cell, or an implanted prosthesis. 32.The light control device of claim 26, wherein the projection unitprojects the excitation light through a waveguide.
 33. A method,comprising: generating, using a light control device, a moving apertureeffect anterior to a retina of an eye at a rate between 50 hertz and 50kilohertz, the generating comprising producing optically one or moreareas anterior to the retina that are characterized by an alteredtransparency, the one or more areas defining one or more apertures thatinclude transparent areas, and the one or more apertures appearing atspatially separated or overlapping positions, at least one of thespatially separated or overlapping positions being non-coaxial with acenter of a pupil of the eye; and using the light control device,sampling and delivering to the retina environmental light from theocular field of view.
 34. The method of claim 33, further comprisingsampling and delivering, using the light control device, approximatelycollimated light from the ocular field of view through at least one ofthe one or more apertures.
 35. The method of claim 33, wherein the lightcontrol device comprises a lens.
 36. The method of claim 33, furthercomprising sampling and delivering, using the light control device,environmental light through at least one of the one or more apertures toa viable cell-containing portion of a diseased or damaged retina. 37.The method of claim 33, further comprising sampling and delivering theenvironmental light from the ocular field of view through at least oneof the one or more apertures to a genetically altered portion of theretina.
 38. The method of claim 33, further comprising sampling anddelivering the environmental light from the ocular field of view throughat least one of the one or more apertures to a portion of the retinathat includes at least one of a retinal transplant, an implanted retinalcell, an implanted stem cell, or an implanted prosthesis.
 39. The methodof claim 33, further comprising sampling and delivering theenvironmental light from the ocular field of view through at least oneof the one or more apertures to an epigenetically altered portion of theretina.
 40. The method of claim 33, further comprising sampling anddelivering the environmental light from the ocular field of view throughat least one of the one or more apertures to a neuroregenerativelyaltered portion of the retina.
 41. The method of claim 33, furthercomprising sampling and delivering, using the light control device,approximately collimated light from the ocular field of view to aportion of the central retina and to a portion of the retina outside thecentral retina, wherein the central retina is centered on the foveola,wherein the central retina contains at least one of a foveola, a fovea,a parafovea, or a macula, and wherein the diameter of the central retinais no greater than 6 mm. 42-49. (canceled)